The most common routes for drug delivery are by oral administration, hypodermic injection, and transdermal delivery. Transdermal delivery is usually painless when compared to hypodermic injection and does not generate dangerous medical waste or pose a risk of disease transmission from needle reuse, which is common in developing countries (Prausnitz et al., 2004). Transdermal delivery also has some advantages over oral routes, which often have poor drug absorption or results in enzymatic degradation in the gastrointestinal tract or liver (Plapied et al., 2011). Transdermal drug delivery devices are typically noninvasive/minimally invasive, can be self-administered, and often result in a high degree of patient compliance. They can also provide an inexpensive drug delivery system with capacity for long-term controlled release.
The United States Food and Drug Administration (USFDA) approved the first transdermal patch in 1981 for scopolamine, a drug that suppresses nausea and vomiting from motion sickness (Gorden et al., 2003). In the United States market, more than 35 transdermal products were introduced during the last two decades, generating total sales of USD 5.7 billion in 2006 (Srodin, 2007). The market is expected to continue to increase as the use transdermal delivery devices are utilized with more substances.
Recently, the advantage of continuous drug delivery has drawn considerable attention over conventional short-term single dose delivery devices, such as those described in U.S. Published application nos. 2007/0225676, 2009/0099502, 2009/0030365, and 2011/0288485. In fact, much research has been done indicating that there are some advantages to continuous drug delivery. For example, research has shown that dyskinesia levels, a motor complication of Parkinson's disease patients, when treated with continuous subcutaneous delivery of ropinrole was lower than that of patients having twice daily oral administration (Stockwell et al., 2008). Clinical studies have also shown that 63% of cancer patients preferred the use of transdermal delivery of fentanyl administrated every 3 days over chronic oral morphine analgesia in pain killing (Sloan et al., 1998). For patients suffering from diabetes mellitus, continuous delivery of human insulin (short acting/regular) could be better than single dose delivery of insulin analogues (long acting), as studies have revealed that the injection of insulin analogues may lead to unexpected outcome (Hemkens et al., 2009). In short, continuous drug delivery has offered some advantages over single dose/bolus therapy in different biomedical applications. Designing a continuous delivery patch that can be loaded with one or more of a variety of drugs and/or analgesics gives rise to a large market potential and greater patient convenience.
Conventional transdermal patches consist of three main components: a backing membrane preventing the drug from dehydration and contamination; a drug reservoir for drug storage therein; and a permeable membrane, directed towards and/or in contact with the skin, that controls the drug diffusion rate across skin. The permeable membrane of the patch can usually be adhered to the skin. The effectiveness of transdermal delivery is usually limited by drug permeability across the lipoidal barrier of the stratum corneum. Drugs that are presently administered across the skin often share three constraining characteristics: low molecular mass (<500 Da), high lipophilicity (oil soluble), and small required dosage (i.e., usually only up to milligram amounts). Opening the transdermal delivery route for large hydrophilic drugs and vaccines is a major challenge, but one that, if overcome, will revolutionize healthcare and medicinal practices. The transdermal delivery of vaccines can avoid not only the use of hypodermic needles (Clenn et al., 2006), but has the potential to improve immune response by targeting the delivery to immunogenic Langerhans cells in skin (Prausnitz et al., 2008).
Most of the transdermal systems currently used are coupled with passive infusion (i.e., drug delivery through a barrier by diffusion), which may not be applicable when significant and precise amounts of drug release are required. Active infusion, a method of drug delivery by forcing a drug-containing liquid into tissues by mechanical means, is thereby a preferred solution. Indeed, studies have shown active infusion with micro-needles is a feasible method for drug delivery (Sivamani et al., 2005). McAllister et al. has demonstrated the use of micro-needles and pressure force (10 psi) to lower 70% of the normalized blood glucose level by insulin delivered in vivo (McAllister et al., 2003). Regulated drug delivery devices were employed by Roxhed et al. with the device having a printed circuit board and Richter et al. used an autonomous pump (Roxhed et al., 2008 and Richter et al., 2004). However, the involvement of the use of battery power hampers the portable usage of the device of Roxhed's design and the pump of Richter's device is probably too bulky to be portable for daily use. The ability to easily sterilize the drug ampoule or other reservoir in patch devices is yet another concern.
The development of a small, disposable, and safe transdermal patch with long-term and consistent or steady drug delivery is therefore highly desirable. The embodiments of the subject invention address these issues in an advantageous design that can be easily manufactured and employed with a variety of substances.